title: Myosin 6 is required for iris development and normal function of the outer retina.
abstract: OBJECTIVE
  To determine the molecular basis and the pathologic consequences of a chemically induced mutation in the translational vision research models 89 (tvrm89) mouse model with ERG defects.
  
  
  METHODS
  Mice from a G3 N-ethyl-N-nitrosourea mutagenesis program were screened for behavioral abnormalities and defects in retinal function by ERGs. The chromosomal position for the recessive tvrm89 mutation was determined in a genome-wide linkage analysis. The critical region was refined, and candidate genes were screened by direct sequencing. The tvrm89 phenotype was characterized by circling behavior, in vivo ocular imaging, detailed ERG-based studies of the retina and RPE, and histological analysis of these structures.
  
  
  RESULTS
  The tvrm89 mutation was localized to a region on chromosome 9 containing Myo6. Sequencing identified a T→C point mutation in the codon for amino acid 480 in Myo6 that converts a leucine to a proline. This mutation does not confer a loss of protein expression levels; however, mice homozygous for the Myo6(tvrm89) mutation display an abnormal iris shape and attenuation of both strobe-flash ERGs and direct-current ERGs by 4 age weeks, neither of which is associated with photoreceptor loss.
  
  
  CONCLUSIONS
  The tvrm89 phenotype mimics that reported for Myosin6-null mice, suggesting that the mutation confers a loss of myosin 6 protein function. The observation that homozygous Myo6(tvrm89) mice display reduced ERG a-wave and b-wave components, as well as components of the ERG attributed to RPE function, indicates that myosin 6 is necessary for the generation of proper responses of the outer retina to light.
authors.affiliation: Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio.
authors.forename: Ivy S
authors.initials: IS
authors.lastname: Samuels
authors.forename: Brent A
authors.initials: BA
authors.lastname: Bell
authors.forename: Gwen
authors.initials: G
authors.lastname: Sturgill-Short
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Ebke
authors.forename: Mary
authors.initials: M
authors.lastname: Rayborn
authors.forename: Lanying
authors.initials: L
authors.lastname: Shi
authors.forename: Patsy M
authors.initials: PM
authors.lastname: Nishina
authors.forename: Neal S
authors.initials: NS
authors.lastname: Peachey
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis; D004596:Electroretinography; D008040:Genetic Linkage; D007498:Iris / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D020125:Mutation, Missense; D018995:Myosin Heavy Chains / Q000235:genetics / Q000502:physiology*; D009887:Ophthalmoscopy; D010641:Phenotype; D012164:Retinal Diseases / Q000235:genetics / Q000503:physiopathology
chemical_list: C089785:myosin VI; D018995:Myosin Heavy Chains
keywords: electroretinography; iris; myosin; retina